Stuart A Lipton

Summary

Publications

  1. pmc MEF2C enhances dopaminergic neuron differentiation of human embryonic stem cells in a parkinsonian rat model
    Eun Gyung Cho
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, La Jolla, California, United States of America
    PLoS ONE 6:e24027. 2011
  2. pmc Redox Regulation of Protein Function via Cysteine S-Nitrosylation and Its Relevance to Neurodegenerative Diseases
    Mohd Waseem Akhtar
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Int J Cell Biol 2012:463756. 2012
  3. pmc S-Nitrosylation of parkin as a novel regulator of p53-mediated neuronal cell death in sporadic Parkinson's disease
    Carmen R Sunico
    Sanford Burnham Medical Research Institute, Del E, Webb Center for Neuroscience, Aging, and Stem Cell Research, 10901, North Torrey Pines Road, La Jolla, CA 92037, USA
    Mol Neurodegener 8:29. 2013
  4. pmc Oxidation of the cysteine-rich regions of parkin perturbs its E3 ligase activity and contributes to protein aggregation
    Fanjun Meng
    Department of Pathology and Anatomical Sciences, Center for Translational Neuroscience, University of Missouri Columbia School of Medicine, Columbia, MO, USA
    Mol Neurodegener 6:34. 2011
  5. pmc Erythropoietin plus insulin-like growth factor-I protects against neuronal damage in a murine model of human immunodeficiency virus-associated neurocognitive disorders
    Yeon Joo Kang
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, La Jolla, CA, USA
    Ann Neurol 68:342-52. 2010
  6. pmc S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury
    Dong Hyung Cho
    Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 324:102-5. 2009
  7. pmc Takusan: a large gene family that regulates synaptic activity
    Shichun Tu
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Neuron 55:69-85. 2007
  8. ncbi request reprint S-nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration
    Takashi Uehara
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Nature 441:513-7. 2006
  9. ncbi request reprint Crosstalk between nitric oxide and zinc pathways to neuronal cell death involving mitochondrial dysfunction and p38-activated K+ channels
    Ella Bossy-Wetzel
    Center for Neuroscience and Aging, The Burnham Institute, La Jolla, CA 92037, USA
    Neuron 41:351-65. 2004
  10. pmc Myocyte enhancer factor 2C as a neurogenic and antiapoptotic transcription factor in murine embryonic stem cells
    Zhen Li
    Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Neurosci 28:6557-68. 2008

Collaborators

Detail Information

Publications77

  1. pmc MEF2C enhances dopaminergic neuron differentiation of human embryonic stem cells in a parkinsonian rat model
    Eun Gyung Cho
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, La Jolla, California, United States of America
    PLoS ONE 6:e24027. 2011
    ..The enriched generation of dopaminergic neuronal lineages from hESCs by forced expression of MEF2CA in the proper context may prove valuable in cell-based therapy for CNS disorders such as PD...
  2. pmc Redox Regulation of Protein Function via Cysteine S-Nitrosylation and Its Relevance to Neurodegenerative Diseases
    Mohd Waseem Akhtar
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Int J Cell Biol 2012:463756. 2012
    ....
  3. pmc S-Nitrosylation of parkin as a novel regulator of p53-mediated neuronal cell death in sporadic Parkinson's disease
    Carmen R Sunico
    Sanford Burnham Medical Research Institute, Del E, Webb Center for Neuroscience, Aging, and Stem Cell Research, 10901, North Torrey Pines Road, La Jolla, CA 92037, USA
    Mol Neurodegener 8:29. 2013
    ..We hypothesized that oxidative posttranslational modification of parkin by environmental toxins may contribute to sporadic PD...
  4. pmc Oxidation of the cysteine-rich regions of parkin perturbs its E3 ligase activity and contributes to protein aggregation
    Fanjun Meng
    Department of Pathology and Anatomical Sciences, Center for Translational Neuroscience, University of Missouri Columbia School of Medicine, Columbia, MO, USA
    Mol Neurodegener 6:34. 2011
    ..abstract:..
  5. pmc Erythropoietin plus insulin-like growth factor-I protects against neuronal damage in a murine model of human immunodeficiency virus-associated neurocognitive disorders
    Yeon Joo Kang
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, La Jolla, CA, USA
    Ann Neurol 68:342-52. 2010
    ..Here, we report that chronic treatment with erythropoietin (EPO) and insulin-like growth factor-I (IGF-I) protects against HIV/gp120-mediated neuronal damage in culture and in vivo...
  6. pmc S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury
    Dong Hyung Cho
    Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 324:102-5. 2009
    ..Preventing nitrosylation of Drp1 by cysteine mutation abrogated these neurotoxic events. SNO-Drp1 is increased in brains of human Alzheimer's disease patients and may thus contribute to the pathogenesis of neurodegeneration...
  7. pmc Takusan: a large gene family that regulates synaptic activity
    Shichun Tu
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Neuron 55:69-85. 2007
    ..Conversely, treating cultured neurons with RNAi targeting alpha-takusan variants resulted in the opposite phenotype. Hence, alpha-takusan represents a large gene family that regulates synaptic activity...
  8. ncbi request reprint S-nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration
    Takashi Uehara
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Nature 441:513-7. 2006
    ..Thus, PDI prevents neurotoxicity associated with ER stress and protein misfolding, but NO blocks this protective effect in neurodegenerative disorders through the S-nitrosylation of PDI...
  9. ncbi request reprint Crosstalk between nitric oxide and zinc pathways to neuronal cell death involving mitochondrial dysfunction and p38-activated K+ channels
    Ella Bossy-Wetzel
    Center for Neuroscience and Aging, The Burnham Institute, La Jolla, CA 92037, USA
    Neuron 41:351-65. 2004
    ..Thus, these data establish a new form of crosstalk between NO and Zn2+ apoptotic signal transduction pathways that may contribute to neurodegeneration...
  10. pmc Myocyte enhancer factor 2C as a neurogenic and antiapoptotic transcription factor in murine embryonic stem cells
    Zhen Li
    Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Neurosci 28:6557-68. 2008
    ....
  11. ncbi request reprint Modulation of NMDA receptor properties and synaptic transmission by the NR3A subunit in mouse hippocampal and cerebrocortical neurons
    Gary Tong
    Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Neurophysiol 99:122-32. 2008
    ..Taken together, these results show that NR3A subunits contribute to NMDAR responses from both synaptic and extrasynaptic receptors, likely composed of NR1, NR2, and NR3 subunits...
  12. pmc Hypoxia enhances S-nitrosylation-mediated NMDA receptor inhibition via a thiol oxygen sensor motif
    Hiroto Takahashi
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Neuron 53:53-64. 2007
    ..These thiols may be nitrosylated preferentially during increasing hypoxia or stroke conditions, thus preventing excessive activity associated with cytotoxicity while avoiding blockade of physiologically active NMDARs...
  13. pmc Neuroprotection by the NR3A subunit of the NMDA receptor
    Nobuki Nakanishi
    Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Neurosci 29:5260-5. 2009
    ..These data suggest that endogenous NR3A protects neurons, and exogenously added NR3A increases neuroprotection and could be potentially exploited as a therapeutic...
  14. pmc Protection of retinal ganglion cells by caspase substrate-binding peptide IQACRG from N-methyl-D-aspartate receptor-mediated excitotoxicity
    Masaaki Seki
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    Invest Ophthalmol Vis Sci 51:1198-207. 2010
    ..Minimally invasive delivery of the peptide to the retina was explored, and the mechanisms of neuroprotection were elucidated...
  15. ncbi request reprint Redox reactions induced by nitrosative stress mediate protein misfolding and mitochondrial dysfunction in neurodegenerative diseases
    Zezong Gu
    Department of Pathology and Anatomical Sciences, University of Missouri Columbia School of Medicine, One Hospital Drive, Columbia, MO 65212, USA
    Mol Neurobiol 41:55-72. 2010
    ....
  16. pmc Balance between synaptic versus extrasynaptic NMDA receptor activity influences inclusions and neurotoxicity of mutant huntingtin
    Shu ichi Okamoto
    Center for Neuroscience, Aging and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, California, USA
    Nat Med 15:1407-13. 2009
    ..Our findings offer a rational therapeutic approach for protecting susceptible neurons in Huntington's disease...
  17. pmc Transcription factor MEF2C influences neural stem/progenitor cell differentiation and maturation in vivo
    Hao Li
    Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 105:9397-402. 2008
    ..Our data support a crucial role for MEF2C in programming early neuronal differentiation and proper distribution within the layers of the neocortex...
  18. doi request reprint HIV/gp120 decreases adult neural progenitor cell proliferation via checkpoint kinase-mediated cell-cycle withdrawal and G1 arrest
    Shu ichi Okamoto
    Center for Neuroscience, Stem Cells, and Aging, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Cell Stem Cell 1:230-6. 2007
    ..Our findings define a molecular mechanism that compromises adult neurogenesis in this neurodegenerative disorder...
  19. pmc A Golgi fragmentation pathway in neurodegeneration
    Saya Nakagomi
    Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Neurobiol Dis 29:221-31. 2008
    ..Taken together, these findings implicate the Golgi as a sensor of stress signals in cell death pathways...
  20. pmc Acute neuroprotective synergy of erythropoietin and insulin-like growth factor I
    Murat Digicaylioglu
    Center for Neuroscience and Aging, The Burnham Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 101:9855-60. 2004
    ..These results imply that EPO+IGF-I exert cooperative actions that afford acute neuroprotection via activation of the PI3-K-Akt pathway...
  21. pmc Aβ induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss
    Maria Talantova
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 110:E2518-27. 2013
    ..Importantly, the improved NMDAR antagonist NitroMemantine, which selectively inhibits extrasynaptic over physiological synaptic NMDAR activity, protects synapses from Aβ-induced damage both in vitro and in vivo. ..
  22. pmc S-nitrosylation of dynamin-related protein 1 mediates mutant huntingtin-induced mitochondrial fragmentation and neuronal injury in Huntington's disease
    Florian Haun
    1 Sanford Burnham Medical Research Institute, Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, La Jolla, California
    Antioxid Redox Signal 19:1173-84. 2013
    ..Here, since aberrant mitochondrial dynamics are also key features of Huntington's disease (HD), we investigated whether formation of SNO-Drp1 contributes to the pathogenesis of HD in cell-based and animal models...
  23. pmc Excitatory glycine responses of CNS myelin mediated by NR1/NR3 "NMDA" receptor subunits
    Juan C Piña-Crespo
    Molecular Neurobiology Laboratory, Salk Institute, and Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, La Jolla, California 92037, USA
    J Neurosci 30:11501-5. 2010
    ..d-Serine responses were abrogated in NR3A-deficient mice. Our results suggest the presence of functional NR1/NR3 receptors in CNS myelin...
  24. pmc Isogenic human iPSC Parkinson's model shows nitrosative stress-induced dysfunction in MEF2-PGC1α transcription
    Scott D Ryan
    Del E Web Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell 155:1351-64. 2013
    ..Furthermore, using small-molecule high-throughput screening, we identify the MEF2C-PGC1α pathway as a therapeutic target to combat PD. ..
  25. pmc Synaptic protein α1-takusan mitigates amyloid-β-induced synaptic loss via interaction with tau and postsynaptic density-95 at postsynaptic sites
    Nobuki Nakanishi
    Del E Web Center for Neuroscience, Aging, and Stem Cell Research, and Bioinformatics Shared Resource, Sanford Burnham Medical Research Institute, La Jolla, California 92037, USA
    J Neurosci 33:14170-83. 2013
    ..In summary, α1-takusan protects synapses from Aβ-induced insult via interaction with PSD-95 and tau. Thus, takusan-based protein sequences from either mouse or human may be of potential therapeutic benefit in AD. ..
  26. pmc Memantine preferentially blocks extrasynaptic over synaptic NMDA receptor currents in hippocampal autapses
    Peng Xia
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, La Jolla, California 92037, USA
    J Neurosci 30:11246-50. 2010
    ..At therapeutic concentrations, memantine effectively blocks excessive extrasynaptic NMDAR-mediated currents, while relatively sparing normal synaptic activity...
  27. pmc Preventing Ca2+-mediated nitrosative stress in neurodegenerative diseases: possible pharmacological strategies
    Tomohiro Nakamura
    Center for Neuroscience, Aging and Stem Cell Research, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell Calcium 47:190-7. 2010
    ..Secondly, therapeutic pro-electrophiles are activated in the face of oxidative insult, thus protecting cells from calcium-induced oxidative stress via the Keap1/Nrf2 transcriptional pathway...
  28. ncbi request reprint Activation of matrix metalloproteinase-9 via neuronal nitric oxide synthase contributes to NMDA-induced retinal ganglion cell death
    Shin Ichi Manabe
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    Invest Ophthalmol Vis Sci 46:4747-53. 2005
    ..This study was designed to investigate the mechanism of excitotoxic retinal ganglion cell (RGC) death in vivo and its relationship to MMP activation...
  29. pmc S-nitrosylation of Drp1 links excessive mitochondrial fission to neuronal injury in neurodegeneration
    Tomohiro Nakamura
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Mitochondrion 10:573-8. 2010
    ..Here, we provide an extended commentary on our findings of nitric oxide-mediated abnormal mitochondrial dynamics...
  30. ncbi request reprint Targeting excitotoxic/free radical signaling pathways for therapeutic intervention in glaucoma
    Masaaki Seki
    Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, CA, USA
    Prog Brain Res 173:495-510. 2008
    ..In this review, we discuss improved memantine derivatives, p38 MAPK, and caspase inhibitors as plausible therapeutics to prevent RGC death...
  31. pmc Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons
    Mark J Barsoum
    Apoptosis and Cell Death Program, Burnham Institute for Medical Research, La Jolla, CA, USA
    EMBO J 25:3900-11. 2006
    ..Importantly, NO-induced neuronal cell death was mitigated by Mfn1 and Drp1(K38A). Thus, persistent mitochondrial fission may play a causal role in NO-mediated neurotoxicity...
  32. ncbi request reprint Subunit-specific roles of glycine-binding domains in activation of NR1/NR3 N-methyl-D-aspartate receptors
    Marc Awobuluyi
    Burnham Institute for Medical Research, 10901 N Torrey Pines Rd, La Jolla, CA 92037, USA
    Mol Pharmacol 71:112-22. 2007
    ..NR3 subunits thus induce plasticity in NR1 with respect to subunit assembly and ligand binding/channel coupling that is unique among ligand-gated ion channel subunits...
  33. ncbi request reprint Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions
    Rajesh Ambasudhan
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell Stem Cell 9:113-8. 2011
    ..Our findings have major implications for cell-replacement strategies in neurodegenerative diseases, disease modeling, and neural developmental studies...
  34. pmc Redox regulation of protein misfolding, mitochondrial dysfunction, synaptic damage, and cell death in neurodegenerative diseases
    Tomohiro Nakamura
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Exp Neurol 238:12-21. 2012
    ..Additionally, high levels of NO can S-nitrosylate a number of aberrant targets involved in neuronal survival pathways, including the antiapoptotic protein XIAP, inhibiting its ability to prevent apoptosis...
  35. ncbi request reprint GC-GAP, a Rho family GTPase-activating protein that interacts with signaling adapters Gab1 and Gab2
    Chunmei Zhao
    Burnham Institute, La Jolla, California 92037, USA
    J Biol Chem 278:34641-53. 2003
    ....
  36. pmc S-nitrosylated SHP-2 contributes to NMDA receptor-mediated excitotoxicity in acute ischemic stroke
    Zhong Qing Shi
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 110:3137-42. 2013
    ..These findings suggest that formation of SNO-SHP-2 represents a key chemical reaction contributing to excitotoxic damage in stroke and potentially other neurological disorders...
  37. pmc ATM-dependent phosphorylation of MEF2D promotes neuronal survival after DNA damage
    Shing Fai Chan
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, and Proteomics Facility, Sanford Burnham Medical Research Institute, La Jolla, California 92037
    J Neurosci 34:4640-53. 2014
    ..Together, our results show that MEF2D is a substrate for phosphorylation by ATM, thus promoting survival in response to DNA damage. Moreover, dysregulation of the ATM-MEF2D pathway may contribute to neurodegeneration in AT. ..
  38. ncbi request reprint S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death
    Zezong Gu
    Center for Neuroscience and Aging, Program in Cell Adhesion and Extracellular Matrix Biology, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 297:1186-90. 2002
    ..These findings suggest a potential extracellular proteolysis pathway to neuronal cell death in which S-nitrosylation activates MMPs, and further oxidation results in a stable posttranslational modification with pathological activity...
  39. ncbi request reprint Human immunodeficiency virus-1/surface glycoprotein 120 induces apoptosis through RNA-activated protein kinase signaling in neurons
    Mehrdad Alirezaei
    Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California 92037, USA
    J Neurosci 27:11047-55. 2007
    ..Together, these results identify PKR as a critical mediator of gp120 neurotoxicity, suggesting that activation of PKR contributes to the neuronal injury and cell death observed in HAD...
  40. ncbi request reprint Characterization and comparison of the NR3A subunit of the NMDA receptor in recombinant systems and primary cortical neurons
    Yasnory F Sasaki
    Center for Neuroscience and Aging, The Burnham Institute, La Jolla, California 92037, USA
    J Neurophysiol 87:2052-63. 2002
    ..Finally, a new longer splice variant of NR3A has been cloned and found to be expressed in rodent cortical neurons by single-cell RT-PCR and in situ hybridization...
  41. pmc Aberrant protein s-nitrosylation in neurodegenerative diseases
    Tomohiro Nakamura
    Del E Web Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Neuron 78:596-614. 2013
    ..Insight into the pathophysiological role of aberrant S-nitrosylation pathways will enhance our understanding of molecular mechanisms leading to neurodegenerative diseases and point to potential therapeutic interventions...
  42. pmc Differential effects of synaptic and extrasynaptic NMDA receptors on Aβ-induced nitric oxide production in cerebrocortical neurons
    Elena Molokanova
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, La Jolla, California 92037
    J Neurosci 34:5023-8. 2014
    ..These results suggest that pharmacological intervention specifically aimed at eNMDARs may decrease Aβ-induced nitrosative stress and thus ameliorate neurotoxic damage to synapses. ..
  43. ncbi request reprint Inflammatory mediators leading to protein misfolding and uncompetitive/fast off-rate drug therapy for neurodegenerative disorders
    Stuart A Lipton
    Neuroscience and Aging Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    Int Rev Neurobiol 82:1-27. 2007
    ..Targeted S-nitrosylation of the NMDA receptor can be achieved by coupling NO to memantine, yielding second-generation "UFO drugs" known as NitroMemantines...
  44. pmc S-Nitrosylation activates Cdk5 and contributes to synaptic spine loss induced by beta-amyloid peptide
    Jing Qu
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 108:14330-5. 2011
    ..These findings suggest that S-nitrosylation of Cdk5 is an aberrant regulatory mechanism of enzyme activity that may contribute to the pathogenesis of AD...
  45. pmc Transnitrosylation of XIAP regulates caspase-dependent neuronal cell death
    Tomohiro Nakamura
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Mol Cell 39:184-95. 2010
    ..These findings provide insights into the regulation of caspase activation in neurodegenerative disorders mediated, at least in part, by nitrosative stress...
  46. ncbi request reprint Contribution of glutamatergic signaling to nitrosative stress-induced protein misfolding in normal brain aging and neurodegenerative diseases
    Tomohiro Nakamura
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Aging Cell 6:351-9. 2007
    ..Here, we present evidence for the hypothesis that NO contributes to normal brain aging and degenerative conditions by S-nitrosylating specific chaperones that would otherwise prevent accumulation of misfolded proteins...
  47. pmc Nitrosative stress linked to sporadic Parkinson's disease: S-nitrosylation of parkin regulates its E3 ubiquitin ligase activity
    Dongdong Yao
    Center for Neuroscience and Aging, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 101:10810-4. 2004
    ..These findings may thus provide a molecular link between free radical toxicity and protein accumulation in sporadic Parkinson's disease...
  48. ncbi request reprint Emerging roles of S-nitrosylation in protein misfolding and neurodegenerative diseases
    Tomohiro Nakamura
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, La Jolla, California 92039, USA
    Antioxid Redox Signal 10:87-101. 2008
    ....
  49. pmc S-nitrosylation of Cdk5: potential implications in amyloid-β-related neurotoxicity in Alzheimer disease
    Jing Qu
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, La Jolla, CA, USA
    Prion 6:364-70. 2012
    ..Thus, together with our previous report, these findings delineate an S-nitrosylation pathway wherein Cdk5/NOS1 interaction enhances SNO-Cdk5 formation, mediating mitochondrial dysfunction and synaptic loss during the etiology of AD...
  50. ncbi request reprint Comment on "S-nitrosylation of parkin regulates ubiquitination and compromises parkin's protective function"
    Stuart A Lipton
    Center for Neuroscience and Aging, Burnham Institute, La Jolla, CA 92037, USA
    Science 308:1870; author reply 1870. 2005
  51. ncbi request reprint NR3A modulates the outer vestibule of the "NMDA" receptor channel
    Akira Wada
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Neurosci 26:13156-66. 2006
    ..This modified channel vestibule may also explain the dominant-negative effect of the NR3 subunit on channel behavior when coexpressed with NR1 and NR2 subunits...
  52. pmc High-frequency hippocampal oscillations activated by optogenetic stimulation of transplanted human ESC-derived neurons
    Juan C Piña-Crespo
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, La Jolla, California 92037, USA
    J Neurosci 32:15837-42. 2012
    ....
  53. pmc Isobaric tagging-based quantification by mass spectrometry of differentially regulated proteins in synaptosomes of HIV/gp120 transgenic mice: implications for HIV-associated neurodegeneration
    Sugato Banerjee
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, La Jolla, CA 92037, USA
    Exp Neurol 236:298-306. 2012
    ....
  54. doi request reprint Cell death: protein misfolding and neurodegenerative diseases
    Tomohiro Nakamura
    Center for Neuroscience, Aging and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Apoptosis 14:455-68. 2009
    ..We discuss how memantine/NitroMemantine can inhibit excessive NMDA receptor activity to ameliorate NO production, protein misfolding, and neurodegeneration...
  55. ncbi request reprint S-nitrosylation-mediated redox transcriptional switch modulates neurogenesis and neuronal cell death
    Shu ichi Okamoto
    Neuroscience and Aging Research Center, Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA Electronic address
    Cell Rep 8:217-28. 2014
    ..Our data define a molecular switch whereby redox-mediated posttranslational modification controls both neurogenesis and neurodegeneration via a single transcriptional signaling cascade. ..
  56. ncbi request reprint Paradigm shift in NMDA receptor antagonist drug development: molecular mechanism of uncompetitive inhibition by memantine in the treatment of Alzheimer's disease and other neurologic disorders
    Stuart A Lipton
    The Scripps Research Institute, and the University of California, San Diego, La Jolla, CA 92037, USA
    J Alzheimers Dis 6:S61-74. 2004
    ..These second-generation drugs take advantage of the fact that the NMDA receptor has other modulatory sites in addition to its ion channel that potentially could also be used for safe but effective clinical intervention...
  57. ncbi request reprint Effect of the ubiquitous transcription factors, SP1 and MAZ, on NMDA receptor subunit type 1 (NR1) expression during neuronal differentiation
    Shu ichi Okamoto
    Center for Neuroscience and Aging, The Burnham Institute, La Jolla, CA 92037, USA
    Brain Res Mol Brain Res 107:89-96. 2002
    ..These findings suggest that SP1 and MAZ mediate enhancement of NR1 promoter activity during neuronal differentiation despite the fact that their binding activity does not change...
  58. ncbi request reprint Brain-specific knock-out of hypoxia-inducible factor-1alpha reduces rather than increases hypoxic-ischemic damage
    Rob Helton
    Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    J Neurosci 25:4099-107. 2005
    ..Furthermore, our data suggest that functional redundancy develops after excluding HIF-1alpha, leading to the preservation of gene expression regulating the majority of other previously characterized HIF-dependent genes...
  59. pmc Endoplasmic reticulum protein BI-1 modulates unfolded protein response signaling and protects against stroke and traumatic brain injury
    Maryla Krajewska
    Sanford Burnham Medical Research Institute, 10901 N Torrey Pines Rd La Jolla, CA 92037, USA
    Brain Res 1370:227-37. 2011
    ....
  60. ncbi request reprint Erythropoietin protects cerebrocortical neurons from HIV-1/gp120-induced damage
    Murat Digicaylioglu
    Center for Neuroscience and Aging Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Neuroreport 15:761-3. 2004
    ..Here we show that EPO protects cerebrocortical neurons against apoptosis induced by HIV-1/gp120...
  61. pmc S-nitrosylation of peroxiredoxin 2 promotes oxidative stress-induced neuronal cell death in Parkinson's disease
    Jianguo Fang
    Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 104:18742-7. 2007
    ..Dopaminergic neurons, which are lost in PD, become particularly vulnerable. Thus, our data provide a direct link between nitrosative/oxidative stress and neurodegenerative disorders such as PD...
  62. pmc Redox regulation of mitochondrial fission, protein misfolding, synaptic damage, and neuronal cell death: potential implications for Alzheimer's and Parkinson's diseases
    Tomohiro Nakamura
    Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Apoptosis 15:1354-63. 2010
    ..For example, S-nitrosylation of parkin disrupts its E3 ubiquitin ligase activity, and thereby affects Lewy body formation and neuronal cell death...
  63. ncbi request reprint The chemical biology of clinically tolerated NMDA receptor antagonists
    Huei Sheng Vincent Chen
    Burnham Institute for Medical Research and the University of California San Diego, La Jolla, California 92037, USA
    J Neurochem 97:1611-26. 2006
    ..These second-generation memantine derivatives are designed as pathologically activated therapeutics, and in preliminary studies appear to have even greater neuroprotective properties than memantine...
  64. pmc Emerging role of protein-protein transnitrosylation in cell signaling pathways
    Tomohiro Nakamura
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, La Jolla, California 92037, USA
    Antioxid Redox Signal 18:239-49. 2013
    ....
  65. pmc S-nitrosylation of critical protein thiols mediates protein misfolding and mitochondrial dysfunction in neurodegenerative diseases
    Tomohiro Nakamura
    Del E Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Antioxid Redox Signal 14:1479-92. 2011
    ....
  66. doi request reprint Mitochondrial dynamics in cell death and neurodegeneration
    Dong Hyung Cho
    Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell Mol Life Sci 67:3435-47. 2010
    ....
  67. pmc Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction by modulating glutamate receptor recycling in Down's syndrome
    Xin Wang
    Center for Neuroscience, Aging and Stem Cell Research, Sanford Burnham Medical Research Institute, La Jolla, California, USA
    Nat Med 19:473-80. 2013
    ..Upregulating SNX27 in the hippocampus of Down's syndrome mice rescues synaptic and cognitive deficits. Our identification of the role of SNX27 in synaptic function establishes a new molecular mechanism of Down's syndrome pathogenesis...
  68. ncbi request reprint Pathologically activated therapeutics for neuroprotection
    Stuart A Lipton
    Burnham Institute for Medical Research, The Salk Institute for Biological Studies, The Scripps Research Institute, and the University of California at San Diego 10901 North Torrey Pines Road, La Jolla, California 29, 037, USA
    Nat Rev Neurosci 8:803-8. 2007
    ..This approach has already met with success, and has led to the development of the potentially neuroprotective drug memantine, an N-methyl-D-aspartate (NMDA)-type and glutamate receptor antagonist...
  69. ncbi request reprint Mechanisms of neuroimmunity and neurodegeneration associated with HIV-1 infection and AIDS
    Marcus Kaul
    Center for Neuroscience and Aging Research, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Neuroimmune Pharmacol 1:138-51. 2006
    ..This article addresses recently uncovered pathologic neuroimmune and degenerative mechanisms contributing to neuronal damage induced by HIV-1 and discusses experimental and potentially future therapeutic approaches...
  70. ncbi request reprint Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond
    Stuart A Lipton
    Burnham Institute for Medical Research, University of California at San Diego, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Drug Discov 5:160-70. 2006
    ....
  71. pmc Rapid induction and long-term self-renewal of primitive neural precursors from human embryonic stem cells by small molecule inhibitors
    Wenlin Li
    Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 108:8299-304. 2011
    ..Our work uniformly captures and maintains primitive neural stem cells from hESCs...
  72. ncbi request reprint Suppression of cyclin-dependent kinase 5 activation by amyloid precursor protein: a novel excitoprotective mechanism involving modulation of tau phosphorylation
    Ping Han
    Center for Neuroscience and Aging, The Burnham Institute, La Jolla, California 92037, USA
    J Neurosci 25:11542-52. 2005
    ..We suggest that CDK5 activation, through a calcium/calpain/p25 pathway, plays a key role in neuronal excitotoxicity and represents an underlying mechanism for the physiological functions of APP...
  73. pmc Failures and successes of NMDA receptor antagonists: molecular basis for the use of open-channel blockers like memantine in the treatment of acute and chronic neurologic insults
    Stuart A Lipton
    The Burnham Institute, and the University of California, San Diego, La Jolla, California 92037, USA
    NeuroRx 1:101-10. 2004
    ..These second-generation drugs take advantage of the fact that the NMDA receptor has other modulatory sites, in addition to its ion channel, that could potentially be used for safe but effective clinical intervention...
  74. ncbi request reprint Pathologically-activated therapeutics for neuroprotection: mechanism of NMDA receptor block by memantine and S-nitrosylation
    Stuart A Lipton
    The Burnham Institute for Medical Research, The Salk Institute for Biological Studies, The Scripps Research Institute, and the University of California San Diego, La Jolla, California 92037, USA
    Curr Drug Targets 8:621-32. 2007
    ..These second-generation drugs take advantage of the fact that the NMDA receptor has other modulatory sites in addition to its ion channel that potentially could also be used for safe but effective clinical intervention...
  75. ncbi request reprint The molecular basis of memantine action in Alzheimer's disease and other neurologic disorders: low-affinity, uncompetitive antagonism
    Stuart A Lipton
    The Burnham Institute, The Salk Institute for Biological Studies, The Scripps Research Institute, and the University of California San Diego, La Jolla, California 92037, USA
    Curr Alzheimer Res 2:155-65. 2005
    ..These second-generation drugs take advantage of the fact that the NMDA receptor has other modulatory sites in addition to its ion channel that potentially could also be used for safe but effective clinical intervention...
  76. doi request reprint Type C botulinum toxin causes degeneration of motoneurons in vivo
    Li Chun Zhao
    Center for Neuroscience, Aging and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    Neuroreport 21:14-8. 2010
    ..Here, we provide experimental evidence that BoNT/C causes a slow degeneration of motoneurons both in vitro and in vivo. This novel form of BoNT/C-induced cell death may require new treatment strategies...